A single variable in a sensory input may extend over a broad range from minimum to maximum values, such as light intensity or contrast in the visual system. In order to maintain a high sensitivity to small changes in the sensory input using neuronal elements that are limited in their discharge frequency, the sensory system may adapt to local, ambient levels of the particular variable in the sensory stimulus (which can also be expressed as after-images). In the mammalian visual system, neurons at and above the level of the retina are highly sensitive to local contrast and presentation of a sustained level of contrast results in adaptation over a period of tens of seconds or longer. This adaptation to contrast results in an increase in differential sensitive to small changes in contrast levels. Contrast adaptation occurs largely in the Cerebral cortex. It is not prominent at the level of the dorsal lateral geniculate nucleus, but can be prominent in the discharge rate of neurons in the primary visual cortex. Our proposal will address the specific cellular mechanisms of contrast adaptation through the use of intracellular recording techniques in vivo and in vitro. In vivo experiments will examine the cellular correlates of contrast adaptation. In particular, the presence and functional consequences of persistent hyperpolarization of the membrane potential in response to prolonged visual stimulation will be examined as well as potential changes in synaptic activity in the postsynaptic neuron. In addition, possible changes in the strength of thalamocortical monosynaptic connections will also be examined. With in vitro experiments, we will examine the precise cellular mechanisms for the generation of hyperpolarization of the membrane potential following prolonged activity as well as for mechanisms of synaptic depression. In particular, the role of Ca/2+ amd Ma/+ activated K/+ currents and ionic pumps will be addressed. These studies will provide us with a cellular level understanding of adaptation in cortical networks and in so doing provide critical information into the physiologic basis of cellular networks underlying visual function.